Effects of unilateral superimposed high-frequency jet ventilation on porcine hemodynamics and gas exchange during one-lung flooding.

BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV) is suitable for respiratory motion reduction and essential for effective lung tumor ablation. Fluid filling of the target lung wing one-lung flooding (OLF) is necessary for therapeutic ultrasound applications. However, whether unilateral SHFJV allows adequate hemodynamics and gas exchange is unclear. AIM: To compared SHFJV with pressure-controlled ventilation (PCV) during OLF by assessing hemodynamics and gas exchange in different animal positions. METHODS: SHFJV or PCV was used alternatingly to ventilate the non-flooded lungs of the 12 anesthetized pigs during OLF. The animal positions were changed from left lateral position to supine position (SP) to right lateral position (RLP) every 30 min. In each position, ventilation was maintained for 15 min in both modalities. Hemodynamic variables and arterial blood gas levels were repeatedly measured. RESULTS: Unilateral SHFJV led to lower carbon dioxide removal than PCV without abnormally elevated carbon dioxide levels. SHFJV slightly decreased oxygenation in SP and RLP compared with PCV; the lowest values of PaO2 and PaO2/FiO2 ratio were found in SP [13.0; interquartile range (IQR): 12.6-5.6 and 32.5 (IQR: 31.5-38.9) kPa]. Conversely, during SHFJV, the shunt fraction was higher in all animal positions (highest in the RLP: 0.30). CONCLUSION: In porcine model, unilateral SHFJV may provide adequate ventilation in different animal positions during OLF. Lower oxygenation and CO2 removal rates compared to PCV did not lead to hypoxia or hypercapnia. SHFJV can be safely used for lung tumor ablation to minimize ventilation-induced lung motion.

Effects of one-lung flooding on porcine haemodynamics and gas exchange.

Background and aim: We established a porcine model of one-lung flooding (OLF) that can be used for research on the use of ultrasound for lung tumour detection, ultrasound-guided transthoracic needle biopsy, and tumour ablation. However, OLF requires one-lung ventilation (OLV) and eliminates the recruitment strategies of the nonventilated lung. During thoracic surgery, OLV alone can be associated with hypoxia, hypercapnia, and right ventricular overload. Here, we examined whether OLF influences haemodynamics and gas exchange indices during and after OLV/OLF compared with OLV/apnoea and two-lung ventilation (TLV) following deflooding. Methods: Fourteen pigs were included in this study: five were allocated to the control group (CO) and nine were assigned to the OLF group (OLF). Assessments of haemodynamics, gas exchange, and lung sonography were performed after baseline measurements, during OLV/apnoea, OLV/OLF, and after deflooding and TLV. The volume of extravascular lung water was also measured. Results: OLF induced no significant deterioration of oxygenation or ventilation during OLF or after deflooding and TLV. Color-coded duplex sonography of the pulmonary artery in the flooded lung demonstrated an oscillating flow that corresponded to intrapulmonary circulatory arrest. After flooding of the nonventilated lung, the partial pressure of O2 in the arterial blood increased and the shunt fraction decreased significantly compared to OLV/apnoea conditions. After deflooding and TLV, haemodynamics and gas exchange indices showed no differences compared to the CO group and baseline values, respectively. Conclusions: OLF is safe to use during acute animal experimentation. No clinically relevant deterioration of haemodynamics or gas exchange occurred during or after OLF. Due to the circulatory arrest in the flooded lung, the right-to-left shunt volume in the nonventilated lung was minimized. Survival experiments are necessary to further assess the utility of this method.

A special double lumen tube for use in pigs is suitable for different lung ventilation conditions.

Previous studies of haemodynamic and blood gas variables during one-lung ventilation in pigs have used a double lumen tube designed for use in humans. However, because of interspecies differences in bronchial anatomy, a special design for pigs is required. In this study, we evaluated a new left-sided double lumen endobronchial tube designed for use in pigs under different lung ventilation conditions. Ten female pigs (weighing 35-40 kg) were transorally intubated, first with a single lumen tube and then with the left-sided double lumen tube for pigs, and mechanically ventilated. Haemodynamic and blood gas variables were recorded before and after intubation with the double lumen tube and before and after one-lung flooding of the left lung with saline solution. Each pig was repositioned (left lateral, to dorsal, to right lateral) every 30 min during one-lung flooding. Bronchoscopy and thoracic radiography were performed at fixed intervals. Blood gas variables during two-lung ventilation were not impaired by intubation with the double lumen endobronchial tube for pigs, compared with intubation with the single lumen tube. Haemodynamic and blood gas variables were not impaired by one-lung flooding. Complete flooding of the left lung was achieved for all pigs. Two-lung ventilation to reventilate the previously flooded lung provided complete air filling for all pigs. Use of this tube resulted in lung separation without obstruction of bronchi or resultant atelectasis. In this study, the new double lumen tube for pigs was safe for one-lung flooding and prevented fluid entry into the non-flooded lung.

MR imaging of pulmonary lung nodules during one lung flooding: first morphological evaluation using an ex vivo human lung model.

OBJECTIVES: Magnetic resonance imaging in pulmonary oncology is limited because of unfavourable physical and physiological conditions in ventilated lung. Previous work showed operability of One Lung Flooding using saline in vivo in MR units, and that valuable conditions for ultrasound and thermal-based interventions exist. Therefore, this study investigates the morphological details of human lung during Lung Flooding to evaluate its further value focusing on MR-guided interventions. MATERIALS AND METHODS: MR imaging was performed on 20 human lung lobes containing lung cancer and metastases. Lobes were intraoperatively flooded with saline and imaged using T1w Gradient Echo and T2 Spin Echo sequences at 1.5 T. Additionally, six patients received pre-operative MRI. RESULTS: During lung flooding, all lung tumours and metastases were visualized and clearly demarked from the surrounding lung parenchyma. The tumour mass appeared hyperintense in T1w and hypointense in T2w MR imaging. Intra-pulmonary bronchial structures were well differentiated in T2w and calcification in T1w MR sequences. CONCLUSION: Superior conditions with new features of lung MRI were found during lung flooding with an unrestricted visualization of malignant nodules and clear demarcation of intra-pulmonary structures. This could lead to new applications of MR-based pulmonary interventions such as laser or focused ultrasound-based thermal ablations.

A simulation study of the HIFU ablation process on lung tumours, showing consequences of atypical acoustic properties in flooded lung.

Recent work has shown that One Lung Flooding (OLF) enables acoustic access to central lung tumours which can be used for non-invasive ablation using therapeutic ultrasound (HIFU). Therefore acoustic properties of flooded lung as a saline-tissue compound was determined in earlier work, which revealed that atypical acoustical condition in lung exists. Their influence on the HIFU ablation process under aspects of clinical requirements has to be investigated before clinical introduction. For this study a MATLAB based ultrasound simulation tool and a customized bioheat solver were used to determine the temporal course of HIFU induced heating with the corresponding ablation zones. This work revealed that due to the low attenuation in flooded lung the heat induction and therefore the lesion size in lung tumours is enhanced. However, HIFU raster ablation schemes should only be used for benign tumours and the volumetric ablation scheme for malignancies. A minimum power density of 0.1Wcm-3 is required during volumetric ablation to radical ablate lung tumours. The simulations indicate that up to 3 T1 (∅ 3cm) tumours with a sufficient margin (>3mm) can be ablated during one flooding session. The ablation margin is dependent upon perfusion, intra-lobular temperature, as well as ablation temperature, and can be adjusted within range of 2-6mm depending on nodule size. The acoustic conditions in flooded lung are beneficial for thermal HIFU ablation in lung but require an individualized HIFU treatment planning.

One-Lung Flooding Enables Ultrasound-Guided Transthoracic Needle Biopsy of Pulmonary Nodules with High Sensitivity.

Ultrasound-guided transthoracic needle biopsy (USgTTNB) can only be used for peripheral tumours that contact the pleura. Sonographic accessibility of the entire lung can be achieved using one-lung flooding. In this study, feasibility, sensitivity and complication rate of USgTTNB of lung nodules after one-lung flooding in an ex vivo and in vivo lung tumour model were assessed. USgTTNB was performed ex vivo after one-lung flooding in 10 resected human lung lobes containing carcinoma or metastasis. USgTTNB after one-lung flooding and simulation of a lung nodule was conducted in vivo in 5 animals. Transthoracic sonography and chest X-ray were obtained 30 min after reventilation. The lungs were examined macroscopically and histopathologically. The pathologic diagnosis was confirmed in 85.7% and 100% of tumours after first and second puncture attempts, respectively. The successful puncture rate in vivo was 90%. Neither pneumothorax nor bleeding was observed. One-lung flooding enables USgTTNB of lung nodules with a high sensitivity and minimal risk of complications in a pre-clinical model.

Effects of HIFU induced cavitation on flooded lung parenchyma.

BACKGROUND: High intensity focused ultrasound (HIFU) has gained clinical interest as a non-invasive local tumour therapy in many organs. In addition, it has been shown that lung cancer can be targeted by HIFU using One-Lung Flooding (OLF). OLF generates a gas free saline-lung compound in one lung wing and therefore acoustic access to central lung tumours. It can be assumed that lung parenchyma is exposed to ultrasound intensities in the pre-focal path and in cases of misguiding. If so, cavitation might be induced in the saline fraction of flooded lung and cause tissue damage. Therefore this study was aimed to determine the thresholds of HIFU induced cavitation and tissue erosion in flooded lung. METHODS: Resected human lung lobes were flooded ex-vivo. HIFU (1,1 MHz) was targeted under sonographic guidance into flooded lung parenchyma. Cavitation events were counted using subharmonic passive cavitation detection (PCD). B-Mode imaging was used to detect cavitation and erosion sonographically. Tissue samples out of the focal zone were analysed histologically. RESULTS: In flooded lung, a PCD and a sonographic cavitation detection threshold of 625 Wcm- 2(pr = 4, 3 MPa) and 3.600 Wcm- 2(pr = 8, 3 MPa) was found. Cavitation in flooded lung appears as blurred hyperechoic focal region, which enhances echogenity with insonation time. Lung parenchyma erosion was detected at intensities above 7.200 Wcm- 2(pr = 10, 9 MPa). CONCLUSIONS: Cavitation occurs in flooded lung parenchyma, which can be detected passively and by B-Mode imaging. Focal intensities required for lung tumour ablation are below levels where erosive events occur. Therefore focal cavitation events can be monitored and potential risk from tissue erosion in flooded lung avoided.

Flooded Lung Generates a Suitable Acoustic Pathway for Transthoracic Application of High Intensity Focused Ultrasound in Liver.

Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.

One-lung flooding reduces the ipsilateral diaphragm motion during mechanical ventilation.

BACKGROUND: Diaphragm motion during spontaneous or mechanical respiration hinders image-guided percutaneous interventions of tumours in lung and upper abdomen. Motion-tracking methods can be applied but increase procedure complexity and procedure time. One-lung flooding (OLF) generates a suitable acoustic pathway to lung tumours and likely suppress diaphragm motion. The aim of this study was to quantify the effect of OLF on ipsilateral diaphragm motion during contralateral one-lung ventilation. METHODS: To measure the diaphragm motion, M-mode ultrasonography of the right hemidiaphragm was performed during spontaneous breathing and mechanical ventilation, as well as after right-side lung flooding, in three pigs. Diaphragm motion was analysed using magnetic resonance images during left-side lung flooding and mechanical ventilation, in four pigs. RESULTS: Double-lung ventilation increased the diaphragm movement in comparison with spontaneous breathing (17.8 ± 4.4 vs. 12.2 ± 3.4 mm, p = 0.014). Diaphragm movement on the flooded side during contralateral one-lung ventilation was significantly reduced compared to that during double-lung ventilation (3.9 ± 1.0 vs. 17.8 ± 4.4 mm, p = 0.041). By analysing the magnetic resonance images, the hemidiaphragm on the flooded side showed an average displacement of 4.2 mm, a maximum displacement of 15 mm close to the ventilated lung and no displacement at the lateral side. CONCLUSION: OLF leads to a drastic reduction of diaphragm motion on the ipsilateral side which implies that targeting and motion compensation algorithms for interventions like high-intensity focused ultrasound ablation of intrapulmonary and hepatic lesions might not be required.

An ex vivo human lung model for ultrasound-guided high-intensity focused ultrasound therapy using lung flooding.

The usability of an ex vivo human lung model for ablation of lung cancer tissue with high-intensity focused ultrasound (HIFU) is described. Lung lobes were flooded with saline, with no gas remaining after complete atelectasis. The tumor was delineated sono-morphologically. Speed of sound, tissue density and ultrasound attenuation were measured for flooded lung and different pulmonary cancer tissues. The acoustic impedance of lung cancer tissue (1.6-1.9 mega-Rayleighs) was higher than that of water, as was its attenuation coefficient (0.31-0.44 dB/cm/MHz) compared with that of the flooded lung (0.12 dB/cm/MHz). After application of HIFU, the temperature in centrally located lung cancer surrounded by the flooded lung increased as high as 80°C, which is sufficient for treatment. On the basis of these preliminary results, ultrasound-guided HIFU ablation of lung cancer, by lung flooding with saline, appears feasible and should be explored in future clinical studies.

Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs.

BACKGROUND: High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models. METHODS: Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure. RESULTS: A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without haemodynamic complications. CONCLUSIONS: High-intensity focused ultrasound with lung flooding produced a thermal effect in an ex vivo human lung carcinoma and in vivo simulated lung tumours in a porcine model. High-intensity focused ultrasound is a potential new strategy for treating lung cancer.

Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model.

BACKGROUND: Sonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours. METHODS: Fourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed. RESULTS: The ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely examined in vivo. There is no residual gas, which interferes with ultrasound. Pulmonary vessels and bronchi are clearly differentiated. Simulated lung lesions can easily be detected inside the lung lobe. CONCLUSIONS: Lung flooding enables complete lung sonography and tumour detection. We have developed a novel method that efficiently uses ultrasound for guiding intraoperative interventions in open and endoscopic lung surgery.

Sealing of pulmonary arteries with LigaSure: in vivo and ex vivo examinations.

OBJECTIVE: The LigaSure device has been demonstrated to be safe for systemic vessels up to 7 mm in diameter, although its use in thoracic surgery remains understudied. We aimed to evaluate the safety of LigaSure for pulmonary artery sealing. METHODS: In 30 cases of open lung lobectomy, 15 small pulmonary arteries (diameter, 3-5 mm) and 15 thick pulmonary arteries (diameter, 6-8 mm) were divided with LigaSure. Before closure of the thoracotomy, the vessel stumps were ligated proximal to the sealing zone, resected, and preserved in formaldehyde for histopathologic examination. In a control group, a similar number and size of pulmonary arteries were suture-ligated. The burst pressure of the pulmonary arteries from the resected lung lobes was measured. RESULTS: The mean burst pressure of small pulmonary arteries was 4.3-fold less after sealing than after ligation (315 ± 213.1 mm Hg vs 1345 ± 256 mm Hg; P < .001), and 6.4-fold less than after ligation of thick pulmonary arteries (156 ± 42.5 mm Hg vs 1007 ± 141.6 mm Hg; P < .001). Sealed pulmonary arteries >5 mm in diameter have a burst pressure that is 50% less than that of smaller arteries (P < .001). In all cases after sealing, the histologic examination demonstrated only a fusion of the adventitia, whereas the intima and media were replaced and invaginated into the vessel lumen. CONCLUSIONS: LigaSure does not result in complete fusion of the wall layers of pulmonary arteries. The pulmonary artery burst pressure after sealing is significantly less compared with conventional suture ligation. It remains unclear whether these findings create a clinical risk of rupture.